Socially induced brain cells in adults: fate activity and regulation

描述（由申请人提供）：哺乳动物大脑在成年期产生新神经元的能力有限。然而，环境和激素刺激可以增加某些大脑区域的神经发生率，这表明这些刺激最终可能用于治疗，以增强受损或患病大脑区域的修复，并恢复行为功能。电鱼作为成年人脑细胞功能和调节的模型具有不同寻常的前景，因为它们控制某些行为的神经回路异常简单且描述良好，而且它们的大脑显示出异常高的细胞增殖率。在NIMH（R 03）资助的试点研究中，研究人员使用电鱼来建立社会环境，糖皮质激素激素，大脑可塑性和沟通行为之间的联系。具体来说，他们证明，将鱼配对在一起和将鱼植入皮质醇都增强了称为啁啾的电通信行为，并增加了控制啁啾行为的大脑区域中的细胞添加和放射状胶质纤维密度。在研究的第二阶段，研究人员提出了四个问题：1）社会诱导细胞的表型命运是什么？在将鱼配对在一起后，他们将用细胞添加（BrdU）和神经元（Hu）和神经胶质（GFAP，S100 B）分化标记物的抗体共同标记大脑。2)新生细胞在啁啾行为中变得活跃吗？研究人员将在鱼的大脑中用细胞添加标记物（BrdU）和立即早期基因蛋白（c-fos）的抗体共同标记，这些蛋白在它们受到啁啾引发刺激后不久就被激活了。3)皮质醇在社会诱导的大脑和行为可塑性中是否起着因果作用？研究人员将同时用社会互动和糖皮质激素受体阻断剂（RU 486）治疗鱼类，然后分析脑细胞增加，放射状胶质纤维密度和啁啾行为。4)在社会交往中，哪些特定的刺激对大脑和行为的可塑性最有效？研究人员将在允许不同程度通信的刺激环境中配对鱼类，然后确定大脑可塑性是否与电通信信号的接收或产生有关。作为一个地区赠款，这一研究项目也将大大加强本科研究人员的培训。这些研究将有助于在一个模型系统中建立成年出生脑细胞的表型、功能和调控，该模型系统有望确定新生细胞如何改变神经回路和行为。在人类中，社会互动可以改善脑损伤的恢复，减缓神经退化的过程。动物研究表明，社会互动的部分好处可能是通过其对新神经元形成的积极影响而实现的。这项研究旨在确定促进新神经元形成的社会互动的具体特征。

DESCRIPTION (provided by applicant): The mammalian brain has a limited ability to generate new neurons during adulthood. However, environmental and hormonal stimuli can increase rates of neurogenesis in certain brain regions, suggesting that such stimuli might eventually be used therapeutically to enhance the repair of damaged or diseased brain regions and restore behavioral function. Electric fish have unusual promise as a model for the function and regulation adult-born brain cells because their neural circuits controlling certain behaviors are unusually simple and well described, and their brains show unusually high rates of cell proliferation. In pilot studies funded by NIMH (R03), the researchers used electric fish to establish links between the social environment, glucocorticoid hormones, brain plasticity and communication behavior. Specifically, they demonstrated that both pairing fish together and implanting fish with cortisol potentiated an electrocommunication behavior termed chirping and increased cell addition and radial glial fiber density in the brain region that controls chirping behavior. In this second stage of the research, the researchers ask four questions: 1) What is the phenotypic fate of socially-induced cells? After pairing fish together, they will co-label brains with antibodies to markers of cell addition (BrdU) and neuronal (Hu) and glial (GFAP, S100B) differentiation. 2) Do newborn cells become active during chirping behavior? The investigators will co-label with antibodies for markers of cell addition (BrdU) and an immediate early gene protein (c-fos) in the brains of fish soon after they are stimulated with chirp-eliciting stimuli. 3) Does cortisol play a causal role in socially-induced plasticity in brain and behavior? The researchers will treat fish simultaneously with social interaction and a glucocorticoid receptor blocker (RU486) and then assay for brain cell addition radial glial fibers density and chirping behavior. 4) What specific stimuli present in social interaction are most effective in causing brain and behavioral plasticity? The researchers will pair fish in stimulus environments that allow for differing degrees of communication and then determine whether brain plasticity is associated with the reception or production of electrocommunication signals. As an AREA grant, this research project would also significantly enhance the training of undergraduate researchers. These studies will help establish the phenotype, functionality, and regulation of adult-born brain cells in a model system that holds promise for determining how newborn cells modify neural circuits and behavior. In humans, social interaction improves the recovery from brain injury and slows the process of neurodegeneration. Animal studies indicate that part of this benefit of social interaction may occur through its positive effect on the formation of new neurons. This research seeks to identify specific features of social interaction that promote new neuron formation.